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Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis.

The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption of one copy of the Cbfa2 gene significantly reduces the number of progenitors for erythroid and myeloid cells.

Pubmed ID: 8622955


  • Wang Q
  • Stacy T
  • Binder M
  • Marin-Padilla M
  • Sharpe AH
  • Speck NA


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

April 16, 1996

Associated Grants

  • Agency: NCI NIH HHS, Id: CA58343
  • Agency: NIAMS NIH HHS, Id: IPO30AR42689
  • Agency: NINDS NIH HHS, Id: NS-22897

Mesh Terms

  • Animals
  • Base Sequence
  • Central Nervous System Diseases
  • Core Binding Factor Alpha 2 Subunit
  • DNA Primers
  • DNA, Complementary
  • DNA-Binding Proteins
  • Erythropoiesis
  • Female
  • Fetal Death
  • Gene Targeting
  • Hematopoiesis
  • Hemorrhage
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation
  • Necrosis
  • Neoplasm Proteins
  • Pregnancy
  • Proto-Oncogene Proteins
  • Proto-Oncogenes
  • Transcription Factors